16-57376022-T-G

Position:

• chr16-57376022-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002996.6(CX3CL1):​c.70+3384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,132 control chromosomes in the GnomAD database, including 41,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (41405 hom., cov: 32)
• Consequence: CX3CL1 NM_002996.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.635

Genes affected

CX3CL1 (HGNC:10647): (C-X3-C motif chemokine ligand 1) This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-57376022-T-G is Benign according to our data. Variant chr16-57376022-T-G is described in ClinVar as [Benign]. Clinvar id is 1259556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CX3CL1	NM_002996.6	c.70+3384T>G		intron_variant		ENST00000006053.7	NP_002987.1
CX3CL1	NM_001304392.3	c.-65+3384T>G		intron_variant			NP_001291321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CX3CL1	ENST00000006053.7	c.70+3384T>G		intron_variant		1	NM_002996.6	ENSP00000006053	P4
CX3CL1	ENST00000563383.1	c.70+3384T>G		intron_variant		5		ENSP00000456830	A2
CX3CL1	ENST00000564948.1	c.70+3384T>G		intron_variant		3		ENSP00000457996

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112014 AN: 152014 Hom.: 41377 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 112099 AN: 152132 Hom.: 41405 Cov.: 32 AF XY: 0.738 AC XY: 54868 AN XY: 74382

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.742

Alfa AF: 0.746 Hom.: 22362

Bravo AF: 0.724

Asia WGS AF: 0.712 AC: 2476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 32234515) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs170364; hg19: chr16-57409934;